Migraine is a major health problem. Approximately 18% of American women and 6% of men are affected by migraine; a neurovascular disorder characterized by recurrent headaches. Increasing evidence suggests that obesity exacerbates migraine in the form of more frequent and severe headaches. Several plausible mechanisms have been proposed to account for the obesity-migraine link including common inflammatory processes, psychological conditions that are co morbid to both disorders, and similar behavioral risk factors. No research to date has examined the impact of behavioral weight loss (BWL) on migraine. BWL programs focused on improving diet and physical activity consistently producing weight losses of 8-10 kg at 6 months which yield significant improvements in cardiovascular health. Weight loss also has beneficial effects on each of the above pathways that purportedly link migraine and obesity. Thus, BWL programs may serve as an innovative approach to treating migraine headaches. Our pilot work suggests that migraine headaches are improved in obese migraineurs after weight loss produced by 1) bariatric surgery and 2) a pilot BWL program. In study 1, migraine days were reduced in 24 severely obese migraineurs from pre- to 6-months post-bariatric surgery, with nearly half of these patients reporting at least a 50% reduction. In study 2, migraine days were reduced by 61% in 8 obese female migraineurs after a 16 wk BWL program. These findings provide justification for testing BWL in a full-scale trial. We propose to conduct a randomized trial to examine the efficacy of BWL as a treatment for migraine. We will randomly assign 140 obese women who have episodic migraine, as confirmed by the study neurologist, and record e 3 headaches and 4-14 headache days during a 4-wk baseline period to 16 weekly group sessions of either: BWL treatment (n=70) or Healthy Living for Migraine Relief (HLMR; n=70) control. BWL will provide a combination of empirically validated diet and exercise prescriptions and BWL strategies. HLMR will provide education on migraine and pharmacological and behavioral (e.g., stress management) treatments. Both groups will use smart phones to record their headaches for 4 wks at a time during pre-treatment, post-treatment (wks 17-20), and the end of a 16 wk weight maintenance period (wks 29-32). Weight and other potential physiological (inflammation), psychological (depression), and behavioral (diet and exercise) mediators of the treatment effect will be assessed at the end of treatment (wk 16) for tests of prospective effects on migraine days at post-treatment. The primary hypothesis is that BWL participants will report greater pre- to post- treatment reductions in number of migraine days than HLMR participants. This project is highly innovative because it is the first to test the efficacy of BWL for treatment of migraine headaches. Given that both migraine and obesity are prevalent, debilitating and costly disorders, findings from this study have the potential to be of important public health benefit. PUBLIC HEALTH RELEVANCE: Migraine is a major public health problem, disproportionately affecting women that involve recurrent and debilitating headache attacks which increase in frequency and severity among patients who are obese. Behavioral weight loss programs are the gold standard treatment for obesity and consistently produce improvements in cardiovascular health, but the impact of these approaches on migraine is unknown. The current study is the first to test whether behavioral weight loss can help improve migraine headaches in women who are obese.